This application claims priority under 35 U.S.C. 119 of Japanese Patent application No. 10-038186, filed Feb. 3, 1998.
This invention provides a simpler process for detecting an increased risk of a fetal chromosomal abnormality, in particular, a simpler process for detecting an increased risk of fetal Down syndrome.
Down syndrome is widely known as a fetal chromosomal abnormality syndrome. The chromosomal abnormality in the case of Down syndrome is an autosomal abnormality and is classified into 21-trisomy type having three 21th chromosomes, 21th-chromosomal translocation type, and mosaic type. The percentages of these types are 95%, 4% and 1%, respectively. Clinical symptoms of Down syndrome are often a typical and characteristic face, a retardation of physical development and a serious mental handicap.
For prenatal diagnosis of Down syndrome, there is generally employed, for example, a method of carrying out amniocentesis in 10 to 20 weeks of gestation, analyzing the chromosomes of cells, and thereby diagnosing whether the fetus has 21-trisomy or not. However, the amniocentesis has a high diagnostic efficiency but is disadvantageous in that it causes abortion with a probability of 0.5 to 1%. There are also methods such as ultrasonic diagnosis and villus examination, but they involves problems such as low reliability and possibility of injury upon a fetus, respectively. In addition, there have been developed various screening methods practiced on the basis of the measurement of the maternal blood components. In particular, there is widely employed a method comprising calculating the degree of risk from the maternal age and the concentrations of xcex1-fetoprotein (AFP), human chorionic gonadotropin (hCG) and unconjugated estriol (uE3) in the maternal blood (Wald N J. Densem J W. Smith D. Klee G G: Four-Marker Serum Screening For Down""s syndrome. Prenat. Diagn. 1994; 14: 707-716). Further, for example, Japanese Patent Application Kohyo No. 8-500181 discloses a process comprising drying the maternal blood of a pregnant woman and then comparing its hCG level with a reference standard value and a process co-using an AFP level value. Japanese Patent No. 2525474 discloses a process for measuring the contents of uE3, progesterone, 16 xcex1-hydroxydehydroepiandrosterone and the like in a maternal serum sample wherein AFP is also measured. JP-A 2-5895 discloses, for example, a process for measuring the concentration of SOD-1 in an extra-cellular body fluid such as the serum, amniotic fluid or the like of a pregnant woman. However, the above processes involve, for example, the following problems: analysis of the measurement results is troublesome, the sensitivity is still as low as 60 to 70%, and the measurement results tend to be affected by maternal conditions such as the body weight, the contraction of diabetes, habit of smoking, etc.
The present invention has been accomplished in view of such circumstances as above, and an object of the present invention is to provide a process for detecting an increased risk of a fetal chromosomal abnormality which is excellent in harmlessness to a pregnant woman and her fetus and has a high reliability of examination results, and a reagent or kit used in said process.
The present invention provides a process for detecting an increased risk of a fetal chromosomal abnormality which comprises separating AFPs present in a body fluid of a pregnant woman on the basis of the difference between or among their sugar chain structures, measuring one or more of AFPs having a specific sugar chain structure, and detecting the increased risk on the basis of a result of the measurement.
The present invention also provides a reagent for detecting an increased risk of a fetal chromosomal abnormality, which comprises a protein capable of recognizing a specific sugar chain of at least one of AFPs and is used for separating AFPs.
The present invention further provides a process for detecting an increased risk of fetal chromosomal abnormality which comprises separating AFPs present in the body fluid of a pregnant woman on the basis of the difference between or among their sugar chain structures, measuring the proportion of one or more of the AFPs which have a specific sugar chain structure, relative to the total AFPs, and detecting the increased risk on the basis of a result of the measurement.
The present invention also provides a kit for detecting an increased risk of a fetal chromosomal abnormality which comprises (1) a lectin capable of recognizing a specific sugar chain of at least one of AFPs and (2) an anti-AFP antibody.
The present invention further provides as kit for detecting an increased risk of a fetal chromosomal abnormality which comprises (1) a lectin capable of recognizing a specific sugar chain of at least one of AFPs, (2) an anti-AFP antibody capable of binding to all AFPs irrespective of whether the lectin binds to AFPs or not and (3) an anti-AFP antibody having a low reactivity with an AFP having the lectin attached thereto but having high reactivity with an AFP to which the lectin does not bind.